Background:

Identification of tumour antigens is crucial for the development of vaccination strategies against hepatocellular carcinoma (HCC). Most studies come from eastern-Asia, where hepatitis-B is the main cause of HCC. However, tumour antigen expression is poorly studied in low-endemic, western areas where the aetiology of HCC differs.

The success of whole-exome sequencing to identify mutations causing single-gene disorders has been well documented. In contrast whole-exome sequencing has so far had limited success in the identification of variants causing more complex phenotypes that seem unlikely to be due to the disruption of a single gene. We describe a family where two male offspring of healthy first cousin parents present a complex phenotype consisting of peripheral neuropathy and bronchiectasis that has not been described previously in the literature. Due to the fact that both children had the same problems in the context of parental consanguinity we hypothesised illness resulted from either X-linked or autosomal recessive inheritance. Through the use of whole-exome sequencing we were able to simplify this complex phenotype and identified a causative mutation (p.R1070*) in the geneperiaxin (PRX), a gene previously shown to cause peripheral neuropathy (Dejerine–Sottas syndrome) when this mutation is present. For the bronchiectasis phenotype we were unable to identify a causal single mutation or compound...

In Canada, the emergence of vector-borne diseases may occur via international movement and subsequent establishment of vectors and pathogens, or via northward spread from endemic areas in the USA. Re-emergence of endemic vector-borne diseases may occur due to climate-driven changes to their geographic range and ecology. Lyme disease, West Nile virus (WNV), and other vector-borne diseases were identified as priority emerging non-enteric zoonoses in Canada in a prioritization exercise conducted by public health stakeholders in 2013. We review and present the state of knowledge on the public health importance of these high priority emerging vector-borne diseases in Canada. Lyme disease is emerging in Canada due to range expansion of the tick vector, which also signals concern for the emergence of human granulocytic anaplasmosis, babesiosis, and Powassan virus. WNV has been established in Canada since 2001, with epidemics of varying intensity in following years linked to climatic drivers. Eastern equine encephalitis virus, Jamestown Canyon virus, snowshoe hare virus, and Cache Valley...

Silk gut processed from the silk glands of the silkworm could be an ideal biodegradable carrier for cell growth factors. We previously demonstrated that polyhedra, microcrystals of Cypovirus 1 polyhedrin, can serve as versatile carrier proteins. Here, we report the generation of a transgenic silkworm that expresses polyhedrin together with human basic fibroblast growth factor (FGF-2) in its posterior silk glands to utilize silk gut as a proteinaceous carrier to protect and slowly release active cell growth factors. In the posterior silk glands, polyhedrin formed polyhedral microcrystals, and FGF-2 became encapsulated within the polyhedra due to a polyhedron-immobilization signal. Silk gut powder prepared from posterior silk glands containing polyhedron-encapsulated FGF-2 stimulated the phosphorylation of p44/p42 MAP kinase and induced the proliferation of serum-starved NIH3T3 cells by releasing bioactive FGF-2. Even after a one-week incubation at 25 °C, significantly higher biological activity of FGF-2 was observed for silk gut powder incorporating polyhedron-encapsulated FGF-2...

RNA methylation occurs in all types of RNA, including ribosomal RNA, transfer RNA (tRNA), messenger RNA and small RNA ubiquitously in both prokaryotes and eukaryotes. In particular, tRNAs are extensively modified in all organisms and contain a variety of different modifications, including methylation, pseudouridylation, thiouridylation, and addition of isopentenyl groups. Despite their systematic identification, the molecular function of many of these modifications is not well understood. Methylation of tRNAs is introduced by tRNA methyltransferases that are specific towards particular tRNAs and target sites. Different types of tRNA methyltransferases have been identified based on their fold and reaction mechanism. Dnmt2, also known as tRNA-aspartic acid methyltransferase 1 (Trdmt1), is a highly conserved cytosine-C5 methyltransferase that introduces the C38 methylation of tRNAAsp in many species, including lower eukaryotes, plants, insects, and humans. Interestingly, Dnmt2 resembles DNA methyltransferases in structure and catalytic mechanism but it was shown in 2006 to function...

The ability to detect and quantify proteins that are predictors of susceptibility (and/or progression or efficacy of treatments) in specific local tissue prior to clinical detection will be immensely helpful to control various disease states. The follow up value for such proteins in late onset, progressive, multifactorial or metastatic diseases is immense. The diagnosis using blood or excretory fluids based detection of such proteins is often proven unsuitable due to release of the protein in fluids by multiple organs. Only the local tissue protein content often serves as a true predictor of the given disease or disorder. Glaucoma refers to a group of late onset, progressive and irreversible blinding diseases where loss of sight occurs without any other previous symptom or pain. In most individuals a significant degree of peripheral vision is lost before the loss is realized. Intervention usually delays its further progression. Glaucoma is frequently associated with elevation in intraocular pressure (IOP). IOP is the only modifiable factor that confers neuroprotection against...

Mucins are high molecular weight glycoproteins and are primarily expressed by the secretory epithelial cells lining respiratory, gastrointestinal and reproductive tracts. Although mucins are thought to protect epithelial surfaces from various physical insults, recent molecular studies have generated interest in their use as diagnostic and therapeutic targets for their role in cancer. In particular, the transmembrane mucins have been implicated in various oncogenic signaling pathways and their de novo expression in certain malignancies renders them very attractive targets. MUC16 (CA125), the best-known biomarker for ovarian cancer, is up regulated in multiple malignancies and is strongly associated with poor prognosis. MUC16 is a type-I transmembrane protein with a heavily glycosylated N-terminal region, a tandem repeat region comprising of approximately 60 repeats of ~156 amino acids each, a transmembrane (TM) domain and a cytoplasmic tail domain (CTD) of 32 amino acids. MUC16 is predicted to harbor ~56 SEA (Sperm protein, Enterokinase and Agrin) domains unlike other mucins such...

A large body of studies has so far supported the notion that childhood traumatic experiences, including physical, sexual and emotional abuse, neglect and separation from caregivers, significantly increase the risk of developing mental and physical illnesses later on in life, but the biological mechanisms mediating this association remain unclear. More specifically, childhood trauma has been suggested to increase vulnerability to several psychiatric disorders, including depression, anxiety, psychosis and post-traumatic stress disorder,as well as several chronic physical health problems, including rheumatoid arthritis, cardiovascular disease, lung disease, metabolic syndrome and cancer. Furthermore, childhood trauma is associated with more unfavourable psychiatric outcomes, such as more recurrent and treatment-resistant depressive disorder and greater risk of suicidal behaviours. Studies in the recent decade have implicated the innate immune system in the relationship between childhood trauma and adulthood disease.

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